Large structural variants in KOLF2.1J are unlikely to compromise neurological disease modelling.
Mallory RyanJustin A McDonoughMichael Emmerson WardMark R CooksonWilliam C SkarnesFlorian T MerklePublished in: bioRxiv : the preprint server for biology (2024)
Gracia-Diaz and colleagues analysed high-density DNA microarray and whole genome sequencing (WGS) data from the KOLF2.1J 'reference' human induced pluripotent stem cell (hiPSC) line 1 , and report the presence of five high-confidence heterozygous copy number variants (CNVs) at least 100kbp in length 2 . Since three of these CNVs span coding genes, some of which have been associated with neurodevelopmental disease, the authors raise the concern that these CNVs may compromise the utility of KOLF2.1J for neurological disease modelling. We appreciate their thorough analysis and thoughtful interpretation, and agree that potential users of this line should be made aware of all cases where KOLF2.1J differs from the reference genome. However, we believe that the benefits from the widespread use of KOLF2.1J outweigh the potential risks that might arise from the identified CNVs.
Keyphrases
- copy number
- mitochondrial dna
- genome wide
- high density
- stem cells
- endothelial cells
- dna methylation
- human health
- high glucose
- machine learning
- risk assessment
- gene expression
- brain injury
- circulating tumor
- electronic health record
- artificial intelligence
- drug induced
- transcription factor
- stress induced
- circulating tumor cells